A High Density SNP Array for the Domestic Horse and Extant Perissodactyla: Utility for Association Mapping, Genetic Diversity, and Phylogeny Studies
and Phylogeny Studies. PLoS Genet 8(1): e1002451. doi:10.1371/journal.pgen.1002451
A High Density SNP Array for the Domestic Horse and Extant Perissodactyla: Utility for Association Mapping, Genetic Diversity, and Phylogeny Studies
Molly E. McCue
Danika L. Bannasch
Jessica L. Petersen
Jessica Gurr
Ernie Bailey
Matthew M. Binns
Ottmar Distl
Ge rard Gue rin
Telhisa Hasegawa
Emmeline W. Hill
Tosso Leeb
Gabriella
Lindgren
M. Cecilia T. Penedo
Knut H. Red
Oliver A. Ryder
June E. Swinburne
Teruaki
Tozaki
Stephanie J. Valberg
Mark Vaudin
Kerstin Lindblad-Toh
Claire M. Wade
James R.
Mickelson
Michel Georges, University of Lie`ge, Belgium
An equine SNP genotyping array was developed and evaluated on a panel of samples representing 14 domestic horse breeds and 18 evolutionarily related species. More than 54,000 polymorphic SNPs provided an average inter-SNP spacing of ,43 kb. The mean minor allele frequency across domestic horse breeds was 0.23, and the number of polymorphic SNPs within breeds ranged from 43,287 to 52,085. Genome-wide linkage disequilibrium (LD) in most breeds declined rapidly over the first 50-100 kb and reached background levels within 1-2 Mb. The extent of LD and the level of inbreeding were highest in the Thoroughbred and lowest in the Mongolian and Quarter Horse. Multidimensional scaling (MDS) analyses demonstrated the tight grouping of individuals within most breeds, close proximity of related breeds, and less tight grouping in admixed breeds. The close relationship between the Przewalski's Horse and the domestic horse was demonstrated by pair-wise genetic distance and MDS. Genotyping of other Perissodactyla (zebras, asses, tapirs, and rhinoceros) was variably successful, with call rates and the number of polymorphic loci varying across taxa. Parsimony analysis placed the modern horse as sister taxa to Equus przewalski. The utility of the SNP array in genome-wide association was confirmed by mapping the known recessive chestnut coat color locus (MC1R) and defining a conserved haplotype of ,750 kb across all breeds. These results demonstrate the high quality of this SNP genotyping resource, its usefulness in diverse genome analyses of the horse, and potential use in related species.
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Funding: The authors wish to acknowledge the following sources of funding: NIH NIAMS 1K08AR055713-01A2 to MEM, USDA CSREES 2008-35205-18766 to JRM,
Morris Animal Foundation D07EQ-500 to JRM, Science Foundation Ireland PIYRA [04-YI1- B539] to EWH, EURYI award to KL-T, Haras Nationaux to GG, Horse
Betting Levy Board and Thoroughbred Breeders Association to JES and MV, and Volkswagen Foundation, Hannover, Germany to OD. The funders had no role in
study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
. These authors contributed equally to this work.
Horses have held a valued place in human civilization for over
5,000 years through service in war, agriculture, sport and
companionship [1]. Over the last several centuries, more than
400 distinct horse breeds have been established by genetic selection
for a wide number of desirable phenotypic traits [2]. In contrast to
other large domestic animal species including cattle, chickens,
sheep, swine, goats and camelids that are selectively bred mainly for
production of food (meat, milk, eggs) or fiber, the domestic horse is
primarily a utilitarian animal - bred for endurance, strength, speed,
and metabolic efficiency [1]. The horses use as a work animal and
We utilized the previously generated horse genome
sequence and a large SNP database to design an ,54,000
SNP assay for use in the domestic horse and related species.
The utility of this SNP array was demonstrated through
genome-wide linkage disequilibrium, inbreeding and genetic
distance measurements within breeds, as well as
multidimensional scaling and parsimony analysis. Association
mapping confirmed a large conserved segment containing
the chestnut coat color locus in domestic horses. We also
assess the utility of the SNP array in related species, including
the Przewalskis Horse, zebras, asses, tapirs, and rhinoceros.
This SNP genotyping tool will facilitate many genetics
applications in equids, including identification of genes for
health and performance traits, and compelling studies of the
origins of the domestic horse, diversity within breeds, and
evolutionary relationships among related species.
means of transport required selection for individuals that were able
to perform daily physical activity even when feedstuffs were scarce.
The natural athleticism of horses and their enforced intensive
exercise regimes makes them outstanding models for study of the
musculoskeletal, cardiovascular and respiratory systems, while their
natural susceptibility and resistance to infectious agents is useful in
studies of the immune system. Understanding the genetic basis for
within and among breed (...truncated)